Clinical Trials Register

Summary
EudraCT Number:	2005-001951-39
Sponsor's Protocol Code Number:	ST1481-DM-04-004
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2005-09-02
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2005-001951-39

A.3

Full title of the trial

"Estudio fase II de Gimatecan (ST1481) como tratamiento de rescate en pacientes con sarcoma de partes blandas avanzado o metastático y recidivados después de un régimen de quimioterapia basado en antraciclinas / ifosfamida"

A.4.1

Sponsor's protocol code number

ST1481-DM-04-004

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A.
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Information not present in EudraCT
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Gimatecan
D.3.2	Product code	ST 1481
D.3.4	Pharmaceutical form	Capsule*
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Gimatecan
D.3.9.1	CAS number	292618-32-7
D.3.9.2	Current sponsor code	ST 1481
D.3.9.3	Other descriptive name	inhibidor de la topoisomerasa I
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Information not present in EudraCT
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Gimatecan
D.3.2	Product code	ST 1481
D.3.4	Pharmaceutical form	Capsule*
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Gimatecan
D.3.9.1	CAS number	292618-32-7
D.3.9.2	Current sponsor code	ST 1481
D.3.9.3	Other descriptive name	inhibidor de la topoisomerasa I
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Information not present in EudraCT
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Gimatecan
D.3.2	Product code	ST 1481
D.3.4	Pharmaceutical form	Capsule*
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Gimatecan
D.3.9.1	CAS number	292618-32-7
D.3.9.2	Current sponsor code	ST 1481
D.3.9.3	Other descriptive name	inhibidor de la topoisomerasa I
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

sarcoma de partes blandas avanzado o metastático

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	8.0
E.1.2	Level	HLGT
E.1.2	Classification code	10041299

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluar la actividad antitumoral del gimatecan en monoterapia administrado de forma oral dentro de un esquema de 5 días consecutivos cada 28 días como tratamiento de rescate en pacientes con sarcoma de partes blandas avanzado o metastásico y pretratados con quimioterapia basada en antraciclinas / ifosfamida

E.2.2

Secondary objectives of the trial

- Evaluar la actividad de acuerdo con un modelo Bayesiano para evaluar específicamente el comportamiento de los diferentes sub-tipos histológicos.

- Evaluar la actividad basada en el tiempo hasta el acontecimiento y los parámetros relacionados con el tiempo.

- Definir el perfil de seguridad del tratamiento con Gimatecan administrado de forma oral durante 5 días consecutivos cada 28 días.

- Definir la adherencia de los pacientes al tratamiento con gimatecan administrado de forma oral durante 5 consecutivos días cada 28 días.

- Realizar evaluaciones farmacocinéticas

- Realizar evaluaciones opcionales de Medicina Translacional descritas en el Protocolo Auxiliar. Estas evaluaciones se realizarán solamente en los pacientes que las consientan firmando una hoja aparte de consentimiento informado

E.2.3

Trial contains a sub-study

Information not present in EudraCT

E.3

Principal inclusion criteria

1. Sarcoma de partes blandas recidivado después de una quimioterapia basada en antraciclinas e ifosfamida. Solamente los siguientes sub-tipos de sarcoma de partes blandas podrán ser incluidos:
- Fibrosarcoma
- Leiomiosarcoma
- Liposarcoma
- Histiocitoma Maligno Fibroso
- Rhabdomiosarcoma
- Sarcoma de Ewing de tejidos blandos
- Sarcoma Sinovial
- Angiosarcoma/hemangiopericitoma
- Tumor maligno de vaina de nervio periférico
- Sarcoma- inclasificable
- Condrosarcoma mesenquimal

2. Al menos una, y no más de dos (incluyendo adyuvante), regímenes de quimioterapia previa para la enfermedad no resecable avanzada o metastásica, incluyendo antraciclinas e ifosfamida. Las antraciclinas y la ifosfamida pueden haber sido administradas simultaneamente o en líneas sucesivas de tratamiento, pero el paciente debe haber recibido ambas o cada una de ellas en cada línea de tratamiento.

3. Clara enfermedad progresiva. En el caso de tratamiento adyuvante previo, la progresión deberá haber ocurrido durante el tratamiento adyuvante o dentro de los 24 meses desde la finalización del tratamiento adyuvante.

4. Edad > ó =18 años.

5. ECOG performance status ≤ 1.

6. Adecuada función hematológica: hemoglobina > ó = 9 gr/dl; neutrófilos > ó = 1.5 x 10^9/L; plaquetas > ó =150 x 10^9/L;

7. FEVI > ó = 50% evaluada por ultrasonidos

8. Adecuada función hepática y renal :
- Fosfatasa alcalina ≤ 1.5 por encima del valor alto de la normalidad, si hay metástasis óseas, las isoenzimas hepáticas deberán ser <1.5 por encima del valor alto de la normalidad
- Bilirrubina total sérica ≤ 1.5 veces por encima del valor alto de la normalidad independientemente de afectación hepática secundaria al tumor
- ALAT, ASAT ≤ 1.5 por encima del valor alto de la normalidad (< ó = 2.5 por encima del valor alto de la normalidad en presencia de afectación hepática)
- Albumina > ó = 2.5 gr/dl
- Creatinina ≤ 1.5mg/dL

9. Todos los tratamientos previos para el sarcoma deberán haber sido discontinuados > ó = 4 semanas antes de la entrada en el estudio y todas las toxicidades agudas (excluyendo la alopecia) de cualquier tratamiento previo deberá estar resuelta de acuerdo con los criterios de toxicidad CTCAE (Versión 3.0) a un Grado ≤1.

10. Esperanza de vida de al menos 3 meses.

11. Evidencia de un documento de consentimiento informado firmado y fechado indicando que el paciente (o su representante legal aceptado) ha sido informado de todos los aspectos pertinentes del estudio.

12. Buena voluntad y capacidad de cumplir con el protocolo del estudio durante la duración del ensayo.

E.4

Principal exclusion criteria

1. Los siguientes sarcomas NO son elegibles:
- Sarcoma del estroma Gastrointestinal (GIST)
- Osteosarcoma de tejidos blandos
- Condrosarcoma (con la excepción de condrosarcoma mesenquimal)
- Carcinosarcomas (tumores mixtos Mullerianos)
- Sarcoma de Kaposi
- Mesotelioma maligno
- Sarcoma de células claras

2. Tratamiento con radioterapia previa > 30% de la medula ósea

3. Infección activa.

4. Cualquier agente investigacional recibido ≤ 4 semanas antes de la entrada en el estudio y/o inclusión concomitante en otro ensayo clínico.

5. Cualquier régimen previo que haya contenido topotecan- o irinotecan o cualquier régimen que contenga un inhibidor investigacional de la topoisomerasa I.

6. Tratamiento previo con quimioterapia a altas dosis que requirieran rescate con células progenitoras hematopoiéticas.

7. Cualquier cirugía previa gastro-intestinal mayor o enfermedad que pudiera alterar la absorción o la motilidad (ej.: úlcera péptica, enfermedad intestinal inflamatoria, intolerancia conocida a la lactosa, síndromes de mal-absorción, sub-oclusión intestinal, cirugía mayor gastrointestinal previa)..

8. Incapacidad de tragar

9. Presencia de trastornos cardíacos graves (insuficiencia cardiaca congestiva, angina de pecho, infarto de miocardio dentro del año antes de la inclusión en el estudio, hipertensión no controlada o arritmia), trastorno neurológico o psiquiátrico.

10. Presencia de enfermedad no controlada intercurrente o cualquier condición en la que a juicio del investigador se colocaría al paciente en un riesgo excesivo o que interfiera con los resultados del estudio.

11. Neoplasia previa concomitante en otra localización, salvo carcinoma basal o escamoso de la piel o carcinoma de cervix in situ en los 5 años previos.

12. Metástasis cerebrales sintomáticas o meningitis carcinomatosa leptomeníngea que requiera tratamiento.

13. Embarazo o lactancia o incapacidad para utilizar métodos adecuados para el control del embarazo

E.5 End points

E.5.1

Primary end point(s)

Tasa de respuesta observada después del tratamiento con Gimatecan administrado oralmente durante 5 días consecutivos cada 28 días.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Information not present in EudraCT

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Information not present in EudraCT

E.8.1.3

Single blind

Information not present in EudraCT

E.8.1.4

Double blind

Information not present in EudraCT

E.8.1.5

Parallel group

Information not present in EudraCT

E.8.1.6

Cross over

Information not present in EudraCT

E.8.1.7

Other

Information not present in EudraCT

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.5

The trial involves multiple Member States

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

Information not present in EudraCT

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

En pacientes respondedores o con enfermedad estable el tratamiento puede ser continuado hasta evidencia de progresión tumoral, aparición de toxicidad, o rechazo de la paciente, a la discreción del investigador.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Information not present in EudraCT

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2005-09-02.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Information not present in EudraCT

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Tratamiento habitual previsto para la patología de que se trate

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2005-12-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2005-10-18

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials